Protein Phosphatase 2A and DNA-dependent Protein Kinase Are Involved in Mediating Rapamycin-induced Akt Phosphorylation

• Authors: Yikun Li, Emory University; Xuerong Wang, Emory University; Ping Yue, Emory University; Hui Tao, Emory University; Suresh S Ramalingam, Emory University; Taofeek K Owonikoko, Emory University; Xingming Deng, Emory University; Ya Wang, Emory University; Haian Fu, Emory University; Fadlo Khuri, Emory University; Shi-Yong Sun, Emory University
• Journal Title: Journal of Biological Chemistry
• Volume: Volume 288, Number 19
• Publisher: American Society for Biochemistry and Molecular Biology | 2013-05-10, Pages 13215-13224
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1074/jbc.M113.463679
• Subjects: Health Sciences, Oncology; Chemistry, Biochemistry; Biology, Molecular
• Keywords: Akt; Cancer Biology; Cancer Therapy; mTOR; PP2A; DNA-PK; Rapamycin

Abstract

Background: The mechanisms underlying rapamycin-induced Akt phosphorylation have not been fully elucidated. Results: Inhibition of PP2A or DNA-PK attenuates or abrogates rapamycin-induced Akt phosphorylation and co-inhibition of mTOR and DNA-PK enhances anticancer activity. Conclusion: PP2A-dependent and DNA-PK-mediated mechanism is involved in rapamycin-induced Akt phosphorylation. Significance: A previously unknown mechanism underlying rapamycin-induced Akt phosphorylation and a novel strategy to enhance mTOR-targeted cancer therapy may be suggested.